A light-dark shift strategy derived from light-responded metabolic behaviors for polyketides production in marine fungus Halorosellinia sp.

Light, as an important environmental signal, generally brings about a broad regulation in fungal metabolism. In this work, we aim to explore the light-responded metabolic rules so as to further develop a feasible and effective light regulation strategy for production of anticancer polyketide 1403C by marine fungus Halorosellinia sp.. Light derived production enhancement of polyketides was first found in shake flask. To further understand this well working black box, light-responded cell growth, polyketides biosynthesis, metabolic behaviors (enzymes activities and organic acids levels) and mycelia morphology were then investigated in 5-L bioreactor. By comparing cultures under constant irradiation and dark conditions, the entire bioprocess was divided into two phases. During 0-60h, light presumably stimulated relevant metabolism to generate sufficient energy, NADPH and carbon skeleton, particularly malonyl-CoA, which was favorable for mycelia growth and polyketides accumulation. After 60h, light did harm to biomass and polyketides production. Consequently, a light-dark shift strategy was proposed and verified in 5-L bioreactor. It led to a maximal 1403C production of 1.67g/L, which was 24% and 74% higher than those obtained under constant irradiation and dark conditions, respectively.